Eccrine Sweat Research Articles

Dermal Duct Tumor: A Diagnostic Dilemma.

Poromas or poroid tumors are a group of rare, benign cutaneous neoplasms derived from the terminal eccrine or apocrine sweat gland duct. There are four poroma variants with overlapping features: dermal duct tumor (DDT), eccrine poroma, hidroacanthoma simplex, and poroid hidradenoma, of which DDT is the least common. Clinically, the variants have a nonspecific appearance and present as solitary dome-shaped papules, plaques, or nodules. They can be indistinguishable from each other and a multitude of differential diagnoses, necessitating a better understanding of the characteristics that make the diagnosis of poroid neoplasms. However, there remains a paucity of information on these lesions, especially DDTs, given their infrequent occurrence. Herein, we review the literature on DDTs with an emphasis on epidemiology, pathogenesis, clinical features, diagnosis, and management.

A Strange Occurrence of Hematohidrosis: A Case Report From Saudi Arabia

Hematohidrosis is a rare disorder of blood excretion from the eccrine sweat gland not associated with an injury or trauma. Although several hypotheses exist to explain such a condition, the etiology of hematohidrosis remains unknown. Psychological stress is strongly linked to the condition, yet patients may present completely healthy with no identifiable etiology. The diagnosis of hematohidrosis can be difficult and requires the exclusion of bleeding disorders, vasculitis, and other disorders. Here, we present a case of hematohidrosis in a 20-year-old female who had almost weekly bloody tears, as well as gum bleeding, ear bleeding, and epistaxis for the past four months. During hospitalization, the patient was thoroughly investigated for an etiology, but no identifiable cause was found. The patient was diagnosed with hematohidrosis and treated with propranolol. Her condition had improved significantly on follow-up.

A row of nodules on the right side of the face

A row of nodules on the right side of the face

Autophagy, not apoptosis, plays a role in lumen formation of eccrine gland organoids.

Background:Sweat secreted by eccrine sweat glands is transported to the skin surface through the lumen. The eccrine sweat gland develops from the initial solid bud to the final gland structure with a lumen, but how the lumen is formed and the mechanism of lumen formation have not yet been fully elucidated. This study aimed to investigate the mechanism of lumen formation of eccrine gland organoids (EGOs).Methods:Human eccrine sweat glands were isolated from the skin for tissue culture, and the primary cultured cells were collected and cultured in Matrigel for 14 days in vitro. EGOs at different development days were collected for hematoxylin and eosin (H&E) staining to observe morphological changes and for immunofluorescence staining of proliferation marker Ki67, cellular motility marker filamentous actin (F-actin), and autophagy marker LC3B. Western blotting was used to detect the expression of Ki67, F-actin, and LC3B. Moreover, apoptosis was detected using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay kit, and the expression of poly (ADP-ribose) polymerase and Caspase-3 was detected by Western blot. In addition, 3-methyladenine (3MA) was used as an autophagy inhibitor to detect whether the formation of sweat glands can be effectively inhibited.Results:The results showed that a single gland cell proliferated rapidly and formed EGOs on day 4. The earliest lumen formation was observed on day 6. From day 8 to day 14, the rate of lumen formation in EGOs increased significantly. The immunofluorescence and Western blot analyses showed that the expression of Ki67 gradually decreased with the increase in days, while the F-actin expression level did not change. Notably, the expression of autophagy marker LC3B was detected in the interior cells of EGOs as the apoptosis signal of EGOs was negative. Compared with the control group, the autophagy inhibitor 3MA can effectively limit the formation rate of the lumen and reduce the inner diameter of EGOs.Conclusion:Using our model of eccrine gland 3D-reconstruction in Matrigel, we determined that autophagy rather than apoptosis plays a role in the lumen formation of EGOs.

Foxa1 mediates eccrine sweat gland development through transcriptional regulation of Na-K-ATPase expression.

Eccrine sweat glands (ESGs) perform critical functions in temperature regulation in humans. Foxa1 plays an important role in ESG maturation and sweat secretion. Its molecular mechanism, however, remains unknown. This study investigated the expression of Foxa1 and Na-K-ATPase (NKA) in rat footpads at different development stages using immunofluorescence staining, qRT-PCR, and immunoblotting. Also, bioinformatics analysis and Foxa1 overexpression and silencing were employed to evaluate Foxa1 regulation of NKA. The results demonstrated that Foxa1 was consistently expressed during the late stages of ESGs and had a significant role in secretory coil maturation during sweat secretion. Furthermore, the mRNA abundance and protein expression of NKA had similar accumulation trends to those of Foxa1, confirming their underlying connections. Bioinformatics analysis revealed that Foxa1 may interact with these two proteins via binding to conserved motifs in their promoter regions. Foxa1 gain-of-function and loss-of-function experiments in Foxa1-modified cells demonstrated that the activities of NKA were dependent on the presence of Foxa1. Collectively, these data provided evidence that Foxa1 may influence ESG development through transcriptional regulation of NKA expression.

A wearable paper-integrated microfluidic device for sequential analysis of sweat based on capillary action

Soft, skin-mounted microfluidic devices can collect microliter volumes of eccrine sweat and are capable ofin situreal-time analysis of different biomarkers to assess physiological state and health.

Cutaneous disorders related to obesity

ObjectiveTo describe the pattern of cutaneous diseases among obese patients.BackgroundObesity is a medical condition in which excess fat has accumulated to the extent that may have an adverse effect on health leading to reduced life expectancy and increased health problems. Obesity results in changes in skin barrier function, sebaceous gland, apocrine and eccrine sweat glands, function, and wound healing.Patients and methodsThis study was done on 212 Egyptian obese patients visiting the Dermatology Outpatient Clinic of Faculty of Medicine, Menoufia University from November 2020 to March 2021.ResultsIn the present study, there was a statistically highly significant difference between females and males regarding acne (P < 0.001). There was a statistically significant difference between females and males regarding androgenic alopecia, atopic dermatitis, and psoriasis (P < 0.05). There was a statistically nonsignificant difference between females and males regarding acanthosis nigricans, skin tags, hidradenitis suppurativa, seborrheic dermatitis, plantar hyperkeratosis, and stretch marks (P > 0.05). Stretch marks were found in 81.6% of females and 87.7% of males. Androgenic alopecia was found in 56.5% of females and 33.9% of males. Acanthosis nigricans was found in 30.6% of females and 44.6% of males. Acne was found in 30.6% of females and 6.2% of males. Of the studied group, 19.8 and 12.3% complained of intertrigo and erythrasma and 10.4% of the studied group complained of delayed wound healing by hospitalization.ConclusionThe results suggest that obesity seems to have numerous complications that affect the skin as it leads to many cutaneous diseases in this sample of Egyptian people.

Production of artificial fingermarks. Part I – Synthetic secretions formulation

Fingermark variability is a critical parameter. To mitigate the effects of this variability, synthetic secretions in the form of simple mixtures of target compounds found in eccrine sweat have been described in the literature, but they are usually reactive towards only a minimal range of detection techniques. If this approach is acceptable for the production of single-technique test strips, such artificial secretions cannot be considered as reliable fingermark simulants because they do not reproduce the complex matrix that makes up real secretions. Research has shown that sebaceous and eccrine compounds are probably present simultaneously in fingermark residue in the form of an emulsion. This paper is the first part of a research project that aims at producing realistic artificial fingermarks containing an extensive range of eccrine and sebaceous compounds. This first study aimed to reproduce and compare two synthetic fingermark residues formulations and assess their potential to be used as fingermark simulants. Spot tests of the artificial secretions were deposited on paper substrates, and their reactivity with four common detection techniques was tested: 1,2-indanedione-zinc, ninhydrin, oil red O, and physical developer. Both formulations showed very good results when processed with the two amino acid reagents, as well as oil red O, and no obvious differences were observed between the two versions. The results obtained with the physical developer were inconsistent and demonstrated that the fundamental working principle of physical developer needs to be further understood. The results were extremely promising as they showed the potential of such reproducible artificial secretions to be used to assess an extensive range of detection techniques, which would be highly beneficial to guarantee better research and quality control in fingermark detection. The use of spot tests to deposit the simulant was shown to be unreliable and a more controllable and reproducible deposition method using an inkjet printer will be presented in the second part of this research.

Cutaneous ciliated cyst: A case report

Cutaneous ciliated cyst are relatively rare benign lesions, found in the dermis or subcutis of the lower extremities of young females in their second and third decades. The cysts are typically lined by ciliated cuboidal to columnar epithelium, showing pseudostratified areas and focal squamous metaplasia is occasionally present. Immunohistochemical studies have demonstrated that the cysts can be PR and ER positive, similar to the epithelia of the fallopian tubes. The pathogenesis of the cyst is yet being studied, some hypotheses have been proposed including the Mullerian heterotopias, ciliated metaplasia of eccrine sweat glands, and embryonic remnants of the cloacal membrane. We report a cutaneous ciliated cyst over the right gluteus area in a 29 year old female. On histologic examination, the cyst was lined by ciliated columnar epithelium, showing occasional papillary projections.

A Skin-Interfaced, Miniaturized Microfluidic Analysis and Delivery System for Colorimetric Measurements of Nutrients in Sweat and Supply of Vitamins Through the Skin.

Nutrients play critical roles in maintaining core physiological functions and in preventing diseases. Technologies for delivering these nutrients and for monitoring their concentrations can help to ensure proper nutritional balance. Eccrine sweat is a potentially attractive class of biofluid for monitoring purposes due to the ability to capture sweat easily and noninvasively from nearly any region of the body using skin‐integrated microfluidic technologies. Here, a miniaturized system of this type is presented that allows simple, rapid colorimetric assessments of the concentrations of multiple essential nutrients in sweat, simultaneously and without any supporting electronics – vitamin C, calcium, zinc, and iron. A transdermal patch integrated directly with the microfluidics supports passive, sustained delivery of these species to the body throughout a period of wear. Comparisons of measurement results to those from traditional lab analysis methods demonstrate the accuracy and reliability of this platform. On‐body tests with human subjects reveal correlations between the time dynamics of concentrations of these nutrients in sweat and those of the corresponding concentrations in blood. Studies conducted before and after consuming certain foods and beverages highlight practical capabilities in monitoring nutritional balance, with strong potential to serve as a basis for guiding personalized dietary choices.

Exertional heat stress and sodium balance: Leaders, followers, and adaptations.

Exertional heat stress presents a different acute challenge to salt balance compared to at rest. Sodium (Na+) and chloride (Cl-) losses during exercise are overwhelmingly driven by eccrine sweat glands (the "leader"), with minimal urinary excretion. Total salt losses are therefore largely influenced by thermoregulatory need, although adaptations from prior heat exposure or altered dietary intake influences sweat gland ion reabsorption, and therefore sweat Na+ ([Na+]sweat) and Cl- concentrations. The hypotheses that body Na+ and Cl- conservation, or their release from osmotically inactive stores, can occur during the timeframe of a single bout of exertional heat stress, has not been studied to date. The consequences of unreplaced Na+ and Cl- losses during exertional heat stress appear limited primarily to their interactions with water balance. However, the water volume ingested is substantially more influential than salt intake on total body water, plasma volume, osmolality, and thermoregulation during exercise. Acute salt and water loading 1-3h prior to exercise can induce isosmotic hyperhydration in situations where this is deemed beneficial. During exercise, only scenarios of whole body [Na+]sweat>75th centile, combined with fluid replacement >80% of losses, are likely to require significant replacement to prevent hyponatremia. Post-exercise, natriuresis resumes as the main regulator of salt losses, with the kidneys (the "follower") working to restore salt balance incurred from any exercise-induced deficit. If such a deficit exceeds usual dietary intake, and rapid restoration of hydration status is desirable, a deliberate increase in salt intake may assist in volume restoration.

Fabrication of a Wearable Flexible Sweat pH Sensor Based on SERS-Active Au/TPU Electrospun Nanofibers.

Development of wearable sensing platforms is essential for the advancement of continuous health monitoring and point-of-care testing. Eccrine sweat pH is an analyte that can be noninvasively measured and used to diagnose and aid in monitoring a wide range of physiological conditions. Surface-enhanced Raman scattering (SERS) offers a rapid, optical technique for fingerprinting of biomarkers present in sweat. In this paper, a mechanically flexible, nanofibrous, SERS-active substrate was fabricated by a combination of electrospinning of thermoplastic polyurethane (TPU) and Au sputter coating. This substrate was then investigated for suitability toward wearable sweat pH sensing after functionalization with two commonly used pH-responsive molecules, 4-mercaptobenzoic acid (4-MBA), and 4-mercaptopyridine (4-MPy). The developed SERS pH sensor was found to have good resolution (0.14 pH units for 4-MBA; 0.51 pH units for 4-MPy), with only 1 μL of sweat required for a measurement, and displayed no statistically significant difference in performance after 35 days (p = 0.361). Additionally, the Au/TPU nanofibrous SERS pH sensors showed fast sweat-absorbing ability as well as good repeatability and reversibility. The proposed methodology offers a facile route for the fabrication of SERS substrates which could also be used to measure a wide range of health biomarkers beyond sweat pH.

Enhancing sweat rate using a novel device for the treatment of congestion in heart failure

Abstract Background Current treatment of fluid retention in heart failure (HF) relies primarily on diuretics. However, adequate decongestion is not achieved in many patients. Purpose To study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate. Methods We used a device designed to enhance fluid and salt loss via the eccrine sweat glands. Skin temperature in the lower body was increased to 35–38°, where the slope of the relationship between temperature and sweat production is linear. With this wearable device, the sweat evaporates instantaneously, thus avoiding the awareness of perspiration. The primary efficacy endpoint was the ability to increase skin temperature to the desired range without elevating the core temperature above normal range. A secondary efficacy endpoint was a clinically meaningful hourly sweat output, defined as ≥150 mL/h. The primary safety endpoint was any procedure-related adverse events. Results We studied 6 normal subjects and 10 HF patients with clinical evidence of congestion and median NT-proBNP of 602 pg/mL [interquartile range 427 to 1719 pg/mL]. Participants underwent 3 treatment sessions of up to 4h. Skin temperature increased to a median of 37.5°C (interquartile range 37.1–37.9°C) with the core temperature remaining unchanged. The median total weight loss during treatment was 219±67 g/h (Figure) with a range of 100–338 g/h. In 77% of cases, the average sweat rate was ≥150 mL/h. Systolic (P=0.25) and diastolic (P=0.48) blood pressure and heart rate (P=0.11) remained unchanged during the procedure. There were no significant changes in renal function and no procedure-related adverse events. Conclusion Enhancing sweat rate was safe and resulted in a clinically meaningful fluid removal and weight loss. Further evaluation of this concept is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AquaPass Inc Weight loss due to sweat

BOTULINUM TOXIN EFFECTIVENESS IN PRIMARY HYPERHIDROSIS PATIENTS

Hyperhidrosis represents pathology of eccrine sweat glands and is manifested by the skin excessive sweating. For patients, living along with hyperhidrosis represents a big challenge, which has a significant impact on numerous aspects of everyday life, as well as on the social and professional lifestyle and psycho-emotional health.

A Large Mass over the Foot due to the Coexistence of an Eccrine Poroma and a Poroid Hidradenoma: A Case Report.

Eccrine poroma and poroid hidradenoma are uncommon benign poroid neoplasms derived from eccrine sweat glands. There are four types of poroid neoplasms according to the position within the skin layer: hidroacanthoma simplex, eccrine poroma, dermal duct tumor, and poroid hidradenoma. Poroid neoplasms usually arise as slow-growing solitary lesions and can present different clinical presentations, such as a foot mass, an ulceration lesion, a solid cyst, a bleeding lesion or suspected melanoma. Extremities are the most common sites, especially hands and feet. However, the coexistence of these two tumors in a single lesion is extremely rare. Surgical excision represents the main treatment and can be curative, preventing malignant changes and recurrence. We describe a rare solitary tumor over the foot with clinical and histopathological features of an association of an eccrine poroma and a poroid hidradenoma that was surgically treated with no recurrence at the midterm follow-up. Level of Evidence IV, Case Report.

Could personalized plantar orthosis change muscle activity during walking?

Eccrine spiradenoma (ES) is a rare benign tumor of the eccrine sweat gland typically located in the dermis and subcutaneous layers of the skin. Recent literature suggests they typically arise from proximal torso and upper extremities and commonly present as painful subcutaneous nodules. Given its scarcity, imaging findings are not well established. We report an interesting case of plantar eccrine spiradenoma describing its imaging features and closest differentials.

332 New Methods for the Functional In Vitro Characterization of Isolated Human Eccrine Sweat Glands

For humans the evaporation chill through sweat secretion by eccrine sweat glands is the main mechanism for the maintenance of body temperature. In hyperhidrosis, the excess sweat formation can lead to unwanted odours that are, if not pathological, mostly prevented by reducing sweat excretion using antiperspirants. However, in vitro neither the evaluation or approval of new antiperspirants, nor basic research on sweat gland physiology can sufficiently be addressed with currently available model systems. For this very reason the development of a new functional model and assay system is of immense importance. It was thus the aim of this study to develop new methods, that enable the functional characterization of whole human eccrine sweat glands in vitro. From human skin, eccrine sweat glands were isolated enzymatically to improve yield and reproducibility. A resazurin-based vitality assay was adapted from rat sweat glands to assess vitality of human sweat glands. Furthermore, visualization of Calcium (Ca2+) currents was established, including a fluorescent Ca2+ flux assay. Using the resazurin-based assay the vitality of the isolated sweat glands now can be easily assessed and compared after isolation and treatment. Subsequently, for the first time Ca2+ currents and contractions of isolated human sweat glands were observed in vitro in the established Ca2+ flux assay. This was achieved by administration of physiological relevant stimuli that were validated by inhibition. Altogether it is now possible to assay Ca2+ currents of isolated human eccrine sweat glands. These Ca2+ currents represent a first step in the cascade that finally leads to the production of sweat. In the future the prerequisites made here could lead to a more sophisticated in vitro human sweat gland model system.

Malignant Nodular Hidradenoma of the Fingertip: A Case Report

Malignant nodular hidradenoma (MNH) is an infrequent, highly malignant tumor derived from eccrine sweat glands. MNH usually occurs on the scalp, trunk, and proximal extremities, and rarely on the hand. A 55-year-old male patient visited clinics with a gradually enlarging painless mass at fingertip. It begins a year ago. Recently, it has grown rapidly and starts ulceration, and bleeding over the past 3 weeks. According to the biopsy report, it has focal necrosis, atypia, atypical mitoses, and nuclear pleomorphism suggested that the mass was MNH. After histological diagnosis, tiny bone erosion was observed in the re-read radiographic finding. For the oncologic evaluation, the patient was transferred to the cancer center. Radical amputation was performed to the residual tumor that might remain based on re-reading of radiographs. MNH of the finger is especially difficult to the diagnosis given its rarity and variable histology. When ulcerative skin lesion and radiographic bone erosion are observed, one should suspect malignancy and makes out a proper therapeutic plan after histologic biopsy.

The combination of hair follicle-specific marker LHX2 and co-expressed marker can distinguish between sweat gland placodes and hair placodes in rat.

Eccrine sweat gland (ESG) and hair follicle (HF) are different skin appendages but share many common development characteristics. Although the morphology of adult ESG and HF is obviously different, it is difficult to distinguish ESG placodes from HFs placodes morphologically. To study the fate determination of ESG and HF, specific antigen markers for ESG placodes and HF placodes must be found first to distinguish them. In the study, we detected the expression of commonly used keratins 4, 5, 7-10, 12, 14, 15, 17-20, 27 and 73, and the reported ESG and HF specific markers, P-cadherin, Lymphoid enhancer factor 1 (LEF1), LIM Homeobox gene 2(LHX2), Na+/K+-ATPase (NKA) and Na+-K+-2Cl- cotransporter 1 (NKCC1) in ESG and HF placodes by single-immunofluorescence staining and double-immunofluorescence staining. To further verify the results of immunofluorescence staining, Western blot (WB) was used to detect the differential antigen and some co-expressed antigens of ESG and HF placodes. The results showed that both ESG and HF placodes expressed K4/5/14/1517/18, P-cadherin and LEF1, neither expressed K7/8/9/10/12/19/20/27/73, NKA or NKCC1. HF placodes specifically expressed LHX2. Combination of LHX2 and co-expressed antigen K14, can distinguish ESG placodes from HF placodes. We conclude that LHX2 is a specific marker for HF placodes, and ESG placodes and HF placodes can be distinguished by double immunofluorescence staining of the specific marker LHX2 and the co-expressed markers, such as K4, K5, K14, K15, K17, K18, P-cadherin and LEF1.

Effect of PACAP on sweat secretion by immortalized human sweat gland cells

The process of sweating plays an important role in the human body, including thermoregulation and maintenance of the environment and health of the skin. It is known that the conditions of hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion and can result in severe skin conditions such as pruritus and erythema, which significantly reduce the patient’s quality of life. However, there are many aspects of the signaling mechanisms in the process of sweating that have not been clarified, and no effective therapies or therapeutic agents have yet been discovered. Previously, it was reported that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes sweating, but details of the underlying mechanism has not been clarified. We used immortalized human eccrine gland cells (NCL-SG3 cell) to investigate how sweat secretion is induced by PACAP. Intracellular Ca2+ levels were increased in these cells following their exposure to physiological concentrations of PACAP. Intracellular Ca2+ was not elevated when cells were concomitantly treated with PA-8, a specific PAC1-R antagonist, suggesting that PAC1-R is involved in the elevation of intracellular Ca2+ levels in response to PACAP treatment. Furthermore, immunocytochemistry experiments showed that aquaporin-5 was translocated from the cytoplasm to the cell membrane by PACAP. These results suggest that PACAP acts on eccrine sweat glands to promote sweat secretion by translocation of aquaporin-5 to the cell membrane in response to increased levels of intracellular Ca2+. These findings also provide a solid basis for future research initiatives to develop new therapies to treat sweating disorders.